Alleviation of hypopigmentary problems (leukoderma) in humans remains, unfortunately, an unresolved problem. Our laboratories have designed superpotent melanotropins that exhibit ultraprolonged biological activity and that are resistant to inactivation by serum enzymes. These melanotropins are 10,000 times more active than Alpha-melanotropin (Alpha-melanocyte stimulating hormone, Alpha-MSH) in stimulating melanin synthesis within follicular melanocytes of mice. Most importantly, we have demonstrated that these melanotropins, when applied topically to skin of the mouse, are transported trandermally and subsequently activate melanogenesis within hair follicles. These results have important implications for the use of melanotropins in the successful treatment of hypopigmentary problems in humans. We plan to do the following: 1) Develop strategies for the synthesis of melanotropic peptides that posses structural characteristics that will allow them to more readily pass through the stratum corneum to the underlying epidermal melanocytes; 2) Develop strategies for the formulation of these melanotropins at different concentrations into vehicles for topical application (transdermal delivery) to the skin or mice; 3) Determine the melanogenic potential of the melanotropin analogs by monitoring follicular melanogenesis in response to subcutaneously injected and topically applied melanotropin analogs; 4) Develop a human (cadaver) skin model for the study of the transdermal delivery of topically applied melanotropic peptides; 5) Determine whether those melanotropins that are successfully delivered transdermally in the mouse are similarly effective in enhancing melanogenesis in both normal and hypopigemented areas of human skin; 6) Determine the possible systemic side effects of melanotropins to ensure the safe use of topically applied melanotropins in humans. The proposed studies may produce valuable clinical approaches for the treatment of the hypomelanoses. An ultimate outcome of these studies may be to provide a rational method for the hormonal stimulation of "suntanning" in humans.